title: CCN4 regulates vascular smooth muscle cell migration and proliferation.
abstract: The migration and proliferation of vascular smooth muscle cells (VSMCs) are essential elements during the development of atherosclerosis and restenosis. An increasing number of studies have reported that extracellular matrix (ECM) proteins, including the CCN protein family, play a significant role in VSMC migration and proliferation. CCN4 is a member of the CCN protein family, which controls cell development and survival in multiple systems of the body. Here, we sought to determine whether CCN4 is involved in VSMC migration and proliferation. We examined the effect of CCN4 using rat cultured VSMCs. In cultured VSMCs, CCN4 stimulated the adhesion and migration of VSMCs in a dose-dependent manner, and this effect was blocked by an antibody for integrin α5β1. CCN4 expression was enhanced by the pro-inflammatory cytokine tumor necrosis factor α (TNF-α). Furthermore, knockdown of CCN4 by siRNA significantly inhibited the VSMC proliferation. CCN4 also could up-regulate the expression level of marker proteins of the VSMCs phenotype. Taken together, these results suggest that CCN4 is involved in the migration and proliferation of VSMCs. Inhibition of CCN4 may provide a promising strategy for the prevention of restenosis after vascular interventions.
authors.affiliation: Department of Vascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Dong
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Lin
authors.forename: Jingbo
authors.initials: J
authors.lastname: Lu
authors.forename: Heng
authors.initials: H
authors.lastname: Wan
authors.forename: Zhongxin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D050197:Atherosclerosis; D055511:CCN Intercellular Signaling Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D023903:Coronary Restenosis; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D039081:Integrin alpha5beta1 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D055511:CCN Intercellular Signaling Proteins; C492066:CCN4 protein, rat; D016326:Extracellular Matrix Proteins; D039081:Integrin alpha5beta1; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha